Influence of Streptozotocin Diabetes on Intestinal 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Activity in the Rat

Studies were undertaken to examine cholesterogenesis in the intestine of streptozotocin-diabetic rats by measuring incorporation of [2¹⁴C] acetate into cholesterol and 3-hydroxy-3-methylglutaryl CoA reductase (HMG-CoA reductase, EC 1.1.1.34) activity. In these diabetic rats, the intestinal mucosal weight and food consumption were markedly high. The incorporation of [2¹⁴ C] acetate into cholesterol was significantly increased in all diabetic intestinal segments. However, the rates of production of fatty acids and carbon dioxide were not affected. Hepatic H MG-CoA reductase activities were markedly reduced during both the diurnal high and low periods in these diabetic rats, and there was no diurnal variation. In contrast, the specific activities of this enzyme in jejunal crypt cells during both the diurnal high and low periods were significantly higher in these diabetic rats without loss of diurnal variation. Total reductase activity per segment of intestine in jejunal and ileal mucosa (villi + crypt cells) was increased in these diabetic rats. Control rats had higher total and specific activity of ileal mucosal (villi + crypt cells) reductase than of jejunal mucosal reductase during the diurnal high period. The jejunal-ileal gradient in reductase activity and the incorporation of [2¹⁴ C] acetate into cholesterol did not change significantly with streptozotocin-diabetic rats. The results indicate that in streptozotocin-diabetic rats, hepatic cholesterogenesis decreases but intestinal synthesis increases.